The project is described at http://www.ccrnp.ncifcrf.gov/toms/patent/nanoprobe/ Rod-tether Nanoprobes are devices consisting of a rigid molecular rod with a flexible molecular tether attached at each end that can be used to detect and/or modify molecules. Each tether tip has a functional group, such as an antibody or oligonucleotide, that recognizes a target molecule. In addition, one tip carries a donor fluorophore and the other carries an acceptor fluorophore. The fluorophores form a pair for Forster Resonance Energy Transfer (FRET). In the absence of the target molecule, the rod keeps the tether arms apart most of the time, while in the presence of the target molecule, both recognizers bind to the target. This holds the donor and acceptor fluorophores close together. Illumination with light excites the donor and the energy is transferred by FRET to the nearby acceptor, which emits a detectable signal. By reducing an ELISA-like assay entirely to the molecular level, complex macroscopic or microfluidic washing and pumping systems can be eliminated. Rod-tether Nanoprobes can detect a wide variety of clinical and biowarfare reagents. The nanoprobes can also be used to rapidly and simply detect, modify and/or destroy endogenous molecules such as proteins and mRNA involved in a broad range of diseases. The simplest ssDNA-detecting nanoprobe has been created. Resources are sought to develop a variety of prototypes. In this past year, variety of new nanoprobe designs were developed.